Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Effects of Oxytocin on Cognitive and Reactive Fear (RAGE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04292444
Recruitment Status : Recruiting
First Posted : March 3, 2020
Last Update Posted : March 12, 2020
Sponsor:
Information provided by (Responsible Party):
Rene Hurlemann, University of Oldenburg

Brief Summary:
The study examines the (sub)regional specificity of anxiolytic oxytocin (OXT) effects on emotional face processing and reactive and cognitive fear. Preliminary data indicate that the Receptor for Advanced Glycation End Products (RAGE) may regulate oxytocin transport into the brain. Thus, the study aims to replicate previous observations of oxytocin effects on the processing of fearful faces in the centro-medial amygdala and to assess whether a RAGE polymorphism (-374 T/A: rs1800624; TT vs. TA/AA), that has been shown to alter transcriptional activity, modulates anxiolytic OXT effects.

Condition or disease Intervention/treatment Phase
Oxytocin Drug: Oxytocin nasal spray Drug: Placebo Phase 1

Detailed Description:

So far, no study examined selective oxytocin (OXT) effects on reactive (midbrain periaqueductal gray (PAG), central amygdala (CeA), hypothalamus, and the midcingulate cortex (MCC)) and cognitive fear (ventromedial prefrontal cortex (vmPFC), posterior cingulate cortex (PCC), hippocampus, and basolateral amygdala) and the reward system (striatum) with high spatial resolution. Previous studies showed that 7T functional magnetic resonance imaging (fMRI) results in a higher spatial resolution and specificity than 3T MRI in these brain regions and would thus allow for a more detailed characterization of the neural effects.

To disentangle (sub)region-specific effects of OXT on task-related activations of the cingulate structures, the amygdala, the striatum, PAG and VMPFC, the investigators plan to acquire ultra-high field 7T fMRI data from healthy male participants while they perform (i) an emotional face matching task and (ii) a flight initiation distance (FID) task involving fast- or slow-attacking virtual predators that elicit distinct activations in the reactive and cognitive fear circuits. Furthermore, participants will be pre-stratified depending on RAGE polymorphisms to elucidate possible RAGE-related differential OXT effects.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: The study is designed as a double-blind, within-subject, placebo-controlled, non-clinical trial and will involve healthy male participants (n = 60), who will be scanned twice in a randomized order after a single dose of intranasal OXT (24 IU) or placebo. Furthermore participants will be pre-stratified based on a RAGE polymorphism (-374 T/A: rs1800624; n = 30 with TT alleles and n = 30 with TA/AA alleles).
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Disentangling Effects of Oxytocin on Cognitive and Reactive Fear and the Moderating Role of the Receptor for Advanced Glycation End-products
Actual Study Start Date : December 13, 2019
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : May 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Oxytocin

Arm Intervention/treatment
Experimental: RAGE polymorphism (TT)
30 participants with the RAGE polymorphism (-374 T/A: rs1800624; TT) will be selected and scanned twice.
Drug: Oxytocin nasal spray
Intranasal administration of 24 International Units oxytocin 30 minutes before the start of the tasks.

Drug: Placebo
The placebo nasal sprays contain identical ingredients except for the peptide itself (30 minutes before the start of the tasks).

Experimental: RAGE polymorphism (TA/AA)
30 participants with the RAGE polymorphism (-374 T/A: rs1800624; TA/AA) will be selected and scanned twice.
Drug: Oxytocin nasal spray
Intranasal administration of 24 International Units oxytocin 30 minutes before the start of the tasks.

Drug: Placebo
The placebo nasal sprays contain identical ingredients except for the peptide itself (30 minutes before the start of the tasks).




Primary Outcome Measures :
  1. Neural substrates of emotion processing, measured via blood-oxygen-level dependent (BOLD) signal in the amygdala and striatum [ Time Frame: 30 minutes after nasal spray administration ]
    Functional magnetic resonance imaging will be performed to measure the BOLD signal in response to emotional face stimuli. The investigators specifically plan to investigate neural responses to emotional faces in amygdala and striatal subregions. The BOLD signal in response to fearful faces relative to neutral faces and happy faces relative to neutral will be compared between the oxytocin and placebo sessions. To examine effects of the Receptor for Advanced Glycation End Products (RAGE), analyses of variance (ANOVAs) with the between subjects factor RAGE polymorphism (-374 T/A: rs1800624; TT vs. TA/AA) will be conducted on the second level. For analyses of fMRI data, default procedures of the software SPM12 will be adapted for ultra-high-field imaging. The family-wise error rate will be used to correct p-values for multiple comparisons and p < .05 will be considered significant.

  2. Neural responses in the flight initiation distance (FID) task [ Time Frame: 45 minutes after nasal spray administration ]
    Functional magnetic resonance imaging will be performed to measure the blood-oxygen-level dependent (BOLD) signal in a flight initiation distance (FID) task, involving fast-, medium- and slow-attacking virtual predators that elicit distinct activations in the reactive and cognitive fear circuits. BOLD signals to different predator velocities will be analyzed. Analyses will focus on regions-of-interest associated with the processing of cognitive fear (vmPFC, PCC, hippocampus, and basolateral amygdala) and reactive fear (midbrain PAG, central amygdala, hypothalamus, and the MCC) and the reward system (striatum). To examine effects of the Receptor for Advanced Glycation End Products (RAGE), ANOVAs with the between-subject factor RAGE polymorphism (-374 T/A: rs1800624; TT vs. TA/AA) will be conducted on the 2nd level. For the fMRI data, default procedures of the software SPM12 will be adapted for ultra-high-field imaging.

  3. Flight distance and difficulty ratings in the flight initiation distance (FID) task [ Time Frame: 45 minutes after nasal spray administration ]
    Behavioral data of the FID task (flight distance and difficulty ratings ) will be analyzed using mixed ANOVAs in the software SPSS with treatment (oxytocin vs. placebo) as within-subject factor and RAGE polymorphism (TT vs. TA/AA) as between-subject factor. Post-hoc t-tests will be Bonferroni-corrected. Behavioral data will be correlated with fMRI data of the FID task.


Secondary Outcome Measures :
  1. Oxytocin concentration in blood plasma [ Time Frame: 10 minutes before nasal spray administration and 75 minutes after nasal spray administration ]
    Blood samples will be collected before and after the nasal spray administration to assess changes in oxytocin concentrations. Oxytocin concentrations will be analyzed using mixed ANOVAs in SPSS with time (pre vs. post) and treatment (oxytocin vs. placebo) as within-subject factors and RAGE polymorphism (TT vs. TA/AA) as between-subject factor.

  2. Concentration of receptor for advanced glycation endproducts (extracellular domain) in blood plasma [ Time Frame: 10 minutes before nasal spray administration ]

    Blood samples will be collected before the nasal spray administration to assess the RAGE (extracellular domain) concentration in blood plasma.

    RAGE concentrations will be compared between RAGE polymorphisms (TT vs. TA/AA) with independent t-tests. Furthermore, the investigators plan to examine if the RAGE concentration moderates the effects of oxytocin on primary and secondary outcomes.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • RAGE polymorphism (-374 T/A: rs1800624; TT vs. TA/AA)
  • healthy male volunteers
  • right handed

Exclusion Criteria:

  • current psychiatric illness
  • current psychiatric medication or psychotherapy
  • MRI contraindication (e.g. metal in body, claustrophobia)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04292444


Contacts
Layout table for location contacts
Contact: Dirk Scheele, PhD +49 (0)228 287 ext 11151 Dirk.Scheele@ukbonn.de
Contact: Marie J Coenjaerts, MSc +49 (0)228 287 ext 19704 Marie.Coenjaerts@ukbonn.de

Locations
Layout table for location information
Germany
Department of Psychiatry and Medical Psychology Recruiting
Bonn, Germany, 53105
Contact: Dirk Scheele, PhD       Dirk.Scheele@ukbonn.de   
Sponsors and Collaborators
University Hospital, Bonn
Investigators
Layout table for investigator information
Principal Investigator: Rene Hurlemann, MSc, MD, PhD University of Oldenburg
Additional Information:
Publications:
Layout table for additonal information
Responsible Party: Rene Hurlemann, Professor for Psychiatry, University of Oldenburg
ClinicalTrials.gov Identifier: NCT04292444    
Other Study ID Numbers: RAGE
First Posted: March 3, 2020    Key Record Dates
Last Update Posted: March 12, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Rene Hurlemann, University of Oldenburg:
fMRI
receptor for advanced glycation end-products (RAGE)
fear
7T MRI
Additional relevant MeSH terms:
Layout table for MeSH terms
Oxytocin
Oxytocics
Reproductive Control Agents
Physiological Effects of Drugs